DDX43

DDX43

The structure of DDX43 protein.

DDX43 is a protein belonging to the DEAD-box RNA helicase family. It is encoded by the DDX43 gene, also known as DEAD-box helicase 43. DDX43 plays a crucial role in RNA metabolism and is involved in various cellular processes, including RNA splicing, translation, and RNA degradation.

Structure and Function

DDX43 consists of several conserved domains, including the DEAD-box helicase domain, which is responsible for its ATP-dependent RNA helicase activity. This domain allows DDX43 to unwind RNA duplexes and facilitate the remodeling of RNA-protein complexes. Additionally, DDX43 contains an RNA-binding domain that enables it to interact with specific RNA molecules.

The ATPase activity of DDX43 is essential for its helicase function. ATP binding and hydrolysis provide the energy required for DDX43 to unwind RNA structures and participate in RNA-related processes. Furthermore, DDX43 has been found to interact with various proteins involved in RNA metabolism, suggesting its involvement in complex RNA regulatory networks.

Role in RNA Metabolism

DDX43 is primarily involved in RNA splicing, a process that removes non-coding regions (introns) from pre-mRNA molecules to generate mature mRNA. It has been shown that DDX43 interacts with spliceosomal components, such as small nuclear ribonucleoproteins (snRNPs), and facilitates the assembly and disassembly of spliceosomes during splicing. This interaction is crucial for the accurate and efficient splicing of pre-mRNA.

Furthermore, DDX43 has been implicated in translation initiation, the process by which ribosomes assemble on mRNA to initiate protein synthesis. It interacts with translation initiation factors and promotes the assembly of the translation initiation complex, facilitating the recruitment of ribosomes to mRNA.

Additionally, DDX43 is involved in RNA degradation pathways, such as nonsense-mediated mRNA decay (NMD). NMD is a quality control mechanism that degrades mRNA molecules containing premature termination codons to prevent the production of truncated and potentially harmful proteins. DDX43 interacts with NMD factors and contributes to the recognition and degradation of aberrant mRNA.

Clinical Significance

Mutations in the DDX43 gene have been associated with various diseases, including neurodevelopmental disorders and cancer. These mutations can disrupt the normal function of DDX43, leading to dysregulation of RNA metabolism and subsequent cellular dysfunction.

Furthermore, altered expression levels of DDX43 have been observed in certain cancers, suggesting its potential as a diagnostic or prognostic marker. Further research is needed to fully understand the role of DDX43 in disease development and progression.

See Also

• RNA helicase
• RNA splicing
• Translation initiation
• Nonsense-mediated mRNA decay